Extended Data Fig. 8: Schematic of the crosstalk between the BM niche and hematopoietic system during physiological aging. | Nature Cell Biology

Extended Data Fig. 8: Schematic of the crosstalk between the BM niche and hematopoietic system during physiological aging.

From: Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing

Extended Data Fig. 8

In youth, HSCs reside primarily in the central marrow where they are maintained by peri-sinusoidal MSC-L and produce a balanced output of all mature cell lineages (Mk, megakaryocytes; Ery, erythrocytes, My, myeloid cells; Ly, lymphoid cells). Abundant peri-arteriolar MSC-S at the endosteum efficiently produce OPr cells that support osteoblast development, ECM deposition and bone formation. With age, numerical loss and functional decline of MSC-S and OPr leads to bone thinning, with the remaining OPr constitutively producing IL-1. Chronic IL-1, in turn, reinforces niche degradation at the endosteum and contributes to dysfunction of the sinusoidal vasculature. Chronic IL-1 also acts in trans on central marrow MSC-L and HSPCs, driving the appearance of an inflammatory iMSC-L subset and steady-state engagement of emergency myelopoiesis (EM) programs with GMP cluster (cGMP) formation. Strikingly, acute IL-1 blockade with Anakinra enables more youthful blood production during 5FU-mediated regeneration, and life-long removal of IL-1 signaling in Il1r1−/− mice maintains MSC-L in a more youthful cell state associated with improved blood production and HSC function.

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